O,O'-dioctadecylpentaerythritol bis(phosphite)

Carcinogenicity

Description of key information

Not carcinogenic; Mosinger (1976)

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: A non-GLP study with limited information on the methodology employed. It is not possible to assess the quality and reliability of the presented results with the information that is available.

Qualifier:

no guideline followed

Principles of method if other than guideline:

20 male and 20 female rats were dosed daily with 100 mg test material in diet for a period of 2 years. Throughout the study animals were observed for appearance and mortality. An interim sacrifice of 3 male and 3 female rats occurred one year after treatment began. All other surviving animals were sacrificed 2 years after treatment began. All animals that were sacrificed were subjected to a full macroscopic as well as histological examination. Any findings noted were compared to historical control data.

GLP compliance:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: International Institute, 25 rue des Colonies - 13008, Marseille, France
- Housing: groups of 5 by sex
- Diet: Laccassagne MAB 1 synthetic feed (ad libitum)

ENVIRONMENTAL CONDITIONS
- Animals were kept in heated and well ventilated rooms

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

DIET PREPARATION
100 mg of test material per kg of Laccaggagne feed powder.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

1 year (3 animals per sex); 2 years (all surviving animals)

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
100 mg/kg
Basis:
other: mg test material per kg diet

No. of animals per sex per dose:

20 males and 20 females

Control animals:

yes, historical

Observations and examinations performed and frequency:

Animals were observed for mortality during the study. Appearance was recorded as well as any remarkable signs observed.

Sacrifice and pathology:

All surviving to scheduled necropsy were subjected to a comlete macroscopical and histological examination.
- The following tissues were sampled: small intestine, large intestine, spleen, liver, stomach, pancreas, adrenal gland, kidney, testicle, uterine or vesicoprostatic fragments, ovaries, lung, heart, cervix, lymph nodes, salivary glands, thyroid, thymus, brain, bone, pituitary gland, sternum, femur, bone marrow, mesenteric lymph node.
- All fragments were fixed with formalin and stained with toluidine blue

- Liver weigths were recorded.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

3 of the animals died prior to scheduled sacrifice

Mortality:

mortality observed, treatment-related

Description (incidence):

3 of the animals died prior to scheduled sacrifice

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no significant changes in body weight noted between treated and control animals

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

The weight of the liver was comparable amongst treated animals and respective controls

Gross pathological findings:

no effects observed

Description (incidence and severity):

No gross changes were noted in treated animals that were not observed in control animals

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No anomalies were recorded

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

only one malignant tumour was noted in animals treated with test material

Relevance of carcinogenic effects / potential:

The test material was concluded to be non carcinogenic.

Bodyweights:

- At autopsy, the treated males weighed from 290 to 410 g. The weight variations of the males were comparable to the variations noted in the control animals. At autopsy the treated female bodyweights varied between 260 to 330 g. These variations were comparable to the control females.

Histological anatomical observations:

- Mycoplsamal chronic bronchopneumopathy was noted in 7 animals. This condition also exists with the same frequency in control animals.

- Suppurative sphenoidal sinusitis was noted in 2 animals with basilar abscess. Such phenomena are also observed in control animals.

- In the digestive tract there was absence of pharyngeal and esophageal lesions, hemorrhagic gastric foci were found in one animals which was also affected by sinusitis. Moreover, an abdominal tumor of the atypical epithelioma type was noted in one animals and a granulomatous inflammatory process in the rectum in another.

- Liver weight variation was consistent in treated and control animals. Other observations of the liver were as follows: hepatic steatosis processes were observed in 7 animals, a reactive start of Küpfer's cells were observed in 2 animals, a liver of cardiac appearance was observed in one animal. However, such processes are also noted in high frequency in the control animals.

- The spleen was found to be hypertrophic or reactive in the animals affected by pulmonary mycoplasmosis

- Hyperplasia of the spleen was noted in 3 animals

- A cystic nephrosis was noted in 2 animals. Such a condition is found in high frequency in the control animals.

- An interstitial adenoma was noted in a testicle of one animal. This conditions was observed frequently in control animals.

- The uterine mucosa of one animals was hyperplastic. This was also noted frequently in female control animals.

- Diencephalomeningeal reactions were observed in the animals affected by sphenoidal sinusitis with basilar abcess. Incidences of this reaction was also recorded in control animals.

Conclusions:

Under the conditions of the study an abdominal tumor was noted; it was an atypical epithelioma. No breast tumor, subcutaneous or hepatic spindle-cell sarcoma, or adenohypophysial adenoma was noted. Thus, only one malignant tumor (2.5 %) in the animals treated with the test material. This was below the rate of incidence in the control animals.

Executive summary:

The carcinogenicity of the test material was determined in a study in which 20 male and 20 female rats were dosed daily with 100 mg test material in diet for a period of 2 years. Throughout the study animals were observed for appearance and mortality. An interim sacrifice of 3 male and 3 female rats occurred one year after treatment began. All other, surviving, animals were sacrificed 2 years after treatment began. All animals that were sacrificed were subjected to a full macroscopic as well as histological examination. Any findings noted were compared to historical control data. Under the conditions of the study 3 animals died prematurely, however, no clinical signs were noted and no significant differences in bodyweights were noted. No remarkable signs were seen at histology other than an abdominal tumor which was noted in one animal which was found to be an atypical epithelioma. No breast tumor, subcutaneous or hepatic spindle-cell sarcoma, or adenohypophysial adenoma was noted. Thus, only one malignant tumor (2.5 %) in the animals treated with the test material. This was below the rate of incidence in the control animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Species:

rat

Quality of whole database:

The study was not conducted to GLP. The report includes limited information on the methodology employed. It is therefore not possible to assess the quality and reliability of the presented results with the information that is available. The study was assigned a reliability score of 4 according to the criteria of Klimisch (1997).

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for carcinogenicity. The effects observed in the one available study are not considered to be toxicologically significant and are below the incidence in the control animals.

Additional information

The carcinogenicity of the test material was determined in Mosinger (1976), in which 20 male and 20 female rats were dosed daily with 100 mg test material in diet for a period of 2 years. Throughout the study animals were observed for appearance and mortality. An interim sacrifice of 3 male and 3 female rats occurred one year after treatment began. All other, surviving, animals were sacrificed 2 years after treatment began. All animals that were sacrificed was subjected to a full macroscopic as well as histological examination. Any findings noted were compared to historical control data. Under the conditions of the study 3 animals died prematurely, however, no clinical signs were noted and no significant differences in bodyweights were noted. No remarkable signs were seen at histology other than an abdominal tumor which was noted in one animal which was found to be an atypical epithelioma. No breast tumor, subcutaneous or hepatic spindle-cell sarcoma, or adenohypophysial adenoma was noted. Thus, only one malignant tumor (2.5%) in the animals treated with the test material. This was below the rate of incidence in the control animals. The study was reported in limited detail (a translated summary of the original study). The study was therefore assigned a reliability score of 4 in accordance with the principles for assessing data quality as defined in Klimisch (1997).

Justification for selection of carcinogenicity via oral route endpoint:
Only one study is available.